Abstract

The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10,20,50 and 100 mg/kg given 1h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0–30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug. 1982 British Pharmacological Society

title = "ANTIARRHYTHMIC EFFECTS OF ORG 6001 IN RATS: CORRELATION WITH PLASMA AND TISSUE DRUG CONCENTRATIONS",

abstract = "The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10,20,50 and 100 mg/kg given 1h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0–30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug. 1982 British Pharmacological Society",

author = "KATHLEEN KANE and FIONA McDONALD and JAMES PARRATT and CEES TIMMER and JAN VINK",

year = "1982",

month = feb

doi = "10.1111/j.1476-5381.1982.tb08789.x",

language = "English",

volume = "75",

pages = "319--323",

journal = "British Journal of Pharmacology",

issn = "0007-1188",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - ANTIARRHYTHMIC EFFECTS OF ORG 6001 IN RATS

T2 - CORRELATION WITH PLASMA AND TISSUE DRUG CONCENTRATIONS

AU - KANE, KATHLEEN

AU - McDONALD, FIONA

AU - PARRATT, JAMES

AU - TIMMER, CEES

AU - VINK, JAN

PY - 1982/2

Y1 - 1982/2

N2 - The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10,20,50 and 100 mg/kg given 1h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0–30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug. 1982 British Pharmacological Society

AB - The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10,20,50 and 100 mg/kg given 1h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0–30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug. 1982 British Pharmacological Society